Alzheimer’s disease (AD) patients show better everyday functioning in a familiar setting, but the... more Alzheimer’s disease (AD) patients show better everyday functioning in a familiar setting, but they have a reduced ability to access con-textual details and episodes associated with a familiar person or environment. This suggests a dysfunction in the neural networks associated with stimulus identification. Using functional magnetic resonance imaging, we investigated the neural activity during the recognition of per-sonally familiar and unfamiliar faces and places among AD patients and elderly controls. We did not find a group difference in the neural activity within brain areas important for perceptual familiarity recognition. Patients showed reduced activation for familiar stimuli in pre-frontal brain areas known to be important for retrieving contextual information for a stimulus when compared with controls. These changes may contribute to how AD patients experience a personally familiar face or place.
Bei der stationären Versorgung betagter Covid-19-Patientinnen und -Patienten muss sich das Klinik... more Bei der stationären Versorgung betagter Covid-19-Patientinnen und -Patienten muss sich das Klinikpersonal des Risikos eines Post-Covid-Delirs bewusst sein. Interdisziplinäre Ansätze sind der Schlüssel zu guten Behandlungsergebnissen, einer Verbesserung der kognitiven Prognose nach Delir sowie einer Begrenzung von Hospitalisierungszeiten. Neben pharmakologischen und nicht-pharmakologischen Therapieaspekten spielen hier strukturelle Rahmenbedingungen und die altersmedizinische Expertise am Standort eine entscheidende Rolle.
Investigating retinal thickness may complement existing biological markers for dementia and other... more Investigating retinal thickness may complement existing biological markers for dementia and other neurodegenerative diseases. Although retinal thinning is predictive for cognitive decline, it remains to be investigated if and how this feature aligns with neurodegeneration elsewhere in the brain, specifically in early disease stages.
Cognitive deficits occur frequently among older people. Because the underlying aetiologies may be... more Cognitive deficits occur frequently among older people. Because the underlying aetiologies may be heterogeneous, diagnostic assessments include clinical and neuropsychological evaluations, as well as the examination of biological markers, such as those derived from brain imaging and cerebrospinal fluid analyses. In many cases, detecting neurodegeneration due to Alzheimer’s disease is a main target, given the disease’s epidemiological importance and the value of early intervention strategies. Familial aggregation of the disease illustrates that even its common sporadic variant is highly heritable. However, important risk polymorphisms, such as the ε4 allele of the apolipoprotein E gene (APOE4), exert their influence on disease development and onset within a complex individual pattern of other genetic risk polimorphisms, but they may not be commercially detectable or even known yet. Therefore, a first-degree family history of Alzheimer’s disease (FH) is a clinically accessible composite characteristic that can be used to approximately account for these risks’ effect on brain structure and metabolism. Relatively little is known about how genetic risks modulate cognitive deterioration and help-seeking behaviour among non-demented people. Understanding the motivational aspects of health-care utilization is important to provide adequate access to all people at risk for cognitive decline and dementia. We therefore investigated whether FH and other mediators predict memory clinic referrals by primary care physicians. We obtained detailed neurocognitive and clinical data from 229 non-demented people (mean age SD: 67.8 10.4 years; range: 44–90 years; 56.3% women; Mini-Mental State Examination: 28.2 1.9) who had been recruited through our university memory clinic. These individuals presented for first-time clinical evaluation after referrals by primary care physicians. Subjects provided written informed consent for inclusion in this study, and the university’s ethics committee approved the study. All subjects underwent routine brain imaging, and 22.7% consented to APOE genotyping (APOE4 allele frequency: 40.4%). Based on the data level, logistic regression, univariate ANCOVA, or multivariate ANCOVA was used to analyze group differences. We modelled FH (positive/negative) and APOE4 allele carrier status (presence/absence of the allele) as between-group factors; age, sex, and educational status were covariates where appropriate. Age was a continuous variable, whereas educational status was operationalized as being a university graduate (39.3%; 16.7 2.3 years of education) or having completed a non-academic apprenticeship (60.7%; 12.5 1.4 years of education). We used SPSS Statistics for Windows version 24.0 (IBM Corp., Armonk, NY, USA) for all analyses. Significance level was set at 0.05. Female sex (B = 0.845; Exp(B) = 2.33; 95% confidence interval (CI): 1.17–4.65; SE = 0.35; P = 0.016), younger age (B = 0.053; Exp(B) = 1.06; 95%CI: 1.02–1.09; SE = 0.02; P = 0.003), and higher educational status (B = 0.930; Exp(B) = 2.54; 95%CI: 1.21–5.32; SE = 0.38; P = 0.014) predicted active referral requests from patients rather than referrals primarily motivated by the primary care physician. APOE4 did not predict a referral request (B = 0.384; Exp(B) = 1.47; 95%CI: 0.29–7.33; SE = 0.82; P = 0.64). There was a notable trend for FH (B = 0.735; Exp(B) = 2.09; 95%CI: 0.96–4.53; SE = 0.40; P = 0.063) predicting an active request, but there was no association between FH and agecorrected memory performance on the Consortium to Establish a Registry of Alzheimer’s Disease assessment battery (F = 0.04; degrees of freedom (d.f.) = 1; P = 0.843) or the Mini-Mental State Examination (F = 2.57, d.f. = 1, P = 0.110). There was also no difference in the Mini-Mental State Examination with regard to age (F = 2.10, d.f. = 1, P = 0.149) or sex (F = 0.05, d.f. = 1, P = 0.821), but people with higher educational status performed better on this screening test (F = 10.05, d.f. = 1, P = 0.002). Educational status was not a significant predictor of reporting fear of becoming demented (F = 0.70;
Objective: Cognitive reserve influences age of onset, speed of progression, and clinical manifest... more Objective: Cognitive reserve influences age of onset, speed of progression, and clinical manifestations of Alzheimer’s disease. We investigated whether cognitive reserve interacts with clinical and neuropsychological parameters in mild cognitive impairment (MCI). Methods: In this cross-sectional study, we recruited 273 people (70.6 ± 10.1 years, 54.6% women) suffering from subjective memory complaints ( n = 65), MCI ( n = 121), or dementia ( n = 87). Patients underwent neuropsychological evaluation, laboratory testing, and brain imaging. Additionally, we obtained information on years of education and help-seeking motivation. Results: MCI patients with a university degree were significantly older than those without (71.6 ± 9.6 vs. 66.9 ± 10.3, p = 0.02). University-educated MCI patients demonstrated superior performance in verbal fluency. Intrinsic help-seeking motivation (self-referral) was associated with higher cognitive reserve. Female MCI patients presented with greater intrinsi...
Differentiating mild cognitive impairment due to a depressive episode from early neurodegeneratio... more Differentiating mild cognitive impairment due to a depressive episode from early neurodegeneration is challenging among older people. Although neuropsychological tests are routine diagnostic assessments in the evaluation of cognitive decline, in contrast to dementia syndromes, they are often perceived as non-specific in the differentiation of affective and neurodegenerative mild cognitive impairment. Furthermore, depression may represent not only a risk factor for developing dementia but also a prodromal symptom of incipient neurodegeneration. In a university memory disorder clinic setting, we investigated 90 middle-aged and older individuals (57.8% women) suffering from mild cognitive impairment, presenting with or without current or previous depressive disorder. Using discriminance analysis and a multivariate analysis of variance, we show that impairments in executive functioning and attention were predictive towards cognitive impairment developed during a depressive episode. Reduced verbal fluency was also predictive towards depression-associated cognitive impairment, whereas memory was relatively preserved in these patients. Our data suggest that in addition to biological markers, specific neuropsychological profiles can be helpful to separate different etiologies of mild cognitive impairment.
There are frequent discussions about the challenges of teaching in medical school, often focusing... more There are frequent discussions about the challenges of teaching in medical school, often focusing on technological aspects or time constraints. The retirement of one of my mentors reminded me that being an inspirational teacher is also important for our students' personal and professional development.
Comprehensive neuropsychological assessments, composed of specific tests targeting different aspe... more Comprehensive neuropsychological assessments, composed of specific tests targeting different aspects of cognition, are standard diagnostic tools to characterise the singleor multidomain impairments due to neurodegeneration, depression, or other brain disorders. Individual test results are frequently corrected for age-related changes in performance, and for the years of formal education, a proxy measure for cognitive reserve, that also comprises occupational attainment and intelligence. Education correction for neurocognitive tests could influence a physician’s decision how to diagnose and treat an individual, and has been used to reclassify demented and nondemented individuals in diagnostic assessments. Others point to education differences in European and American populations to explain heterogeneous performances in a common screening test for cognitive impairment. Both scenarios imply that we expect a well-educated person to perform better, reflected by a correlation between the years of formal education and cognitive abilities. We hypothesised that generational differences in education opportunities would challenge this assumption. In the 20th century, many societies experienced substantial changes in education opportunities, specifically regarding access to university education. This is reflected by an increasing percentage of university students in these populations and a strong shift in the ratio of men and women attending the institutions. In Germany for example, ‘universities of applied sciences’ have complemented the higher education sector since the 1970s, increasing tertiary education possibilities in addition to other quantitative changes in the education system. Furthermore, over the course of the last century, high tertiary education inequality due to social class effects has been substantially declining, specifically for women. We investigated 276 people (age range 44–94 years, median: 73 years, 124 male, 152 female), presenting for the first time to a German university memory clinic with cognitive impairment in the spectrum from subjective complaints to dementia. Written informed consent was obtained in accordance with the university’s ethics committee requirements. In addition to an interview (with caregiver, if available) and examination by an experienced physician, all patients underwent routine laboratory testing, magnetic resonance brain imaging and detailed neuropsychological assessments, in line with standard guidelines for how to evaluate cognitive impairment. We performed the statistical analyses using SPSS 24.0 (IBM, Armonk, NY, USA), with a significance level of P < 0.05, two-sided, for all analyses. Participants reporting university education (n = 101) compared with all other individuals (n = 175) were more likely to be older, male, and intrinsically motivated for diagnostic assessments, possibly reflecting the protective effect of cognitive reserve, gender differences in education opportunities, and greater dementia worries. We also found weak to moderate correlations between the years of formal education and a multiple choice vocabulary test, a common measure of premorbid intelligence. The correlation strength shows a notable trend for linear decline with increasing age (from Pearson’s r = 0.60, P = 0.01 among our youngest subjects to Pearson’s r = 0.30, P = 0.02 in our oldest participants, Fisher’s z-transformation: z = 1.38, P = 0.08). However, this can only be detected among subjects without university education (patients younger than 65 years: Pearson’s r = 0.39, P < 0.01; patients older than 65 years: Pearson’s r = 0.12, P = 0.28, z = 1.50, P = 0.07), but not among those individuals with university education (patients younger than 65 years Pearson’s r = 0.20, P = 0.46; patients older than 65 years: Pearson’s r = 0.30, P = 0.02, z = 0.35, P = 0.37). When investigating patients with dementia only, we did not observe the effect. The multiple choice vocabulary test is a valid measure of global premorbid intelligence, appropriately insensitive for the influence of neuropsychiatric disease. Considering the test’s limitations, our data would be in line with reduced validity in the case of severe brain disease. However, neither aging nor the presence of cognitive impairment per se sufficiently explained the observed results. We may speculate that older
ZusammenfassungVitamin-B12- und Folsäuremangelzustände sind insbesondere im höheren Lebensalter h... more ZusammenfassungVitamin-B12- und Folsäuremangelzustände sind insbesondere im höheren Lebensalter häufig. Da derartige Mangelzustände relevant dyskognitive Faktoren darstellen, ist ihre Bestimmung in der diagnostischen Abklärung kognitiver Störung bedeutsam und unverzichtbarer Bestandteil der Routinediagnostik in einer Gedächtnisambulanz. Wir geben einen Überblick über den klinischen Stellenwert von Vitamin-B12- und Folsäuremangelzuständen im Kontext kognitiver Störungen und über diesbezüglich relevante diagnostische und therapeutische Aspekte. Die Literaturübersicht wird durch eine Datenanalyse einer Kohorte von 250 Patienten aus unserer Gedächtnisambulanz ergänzt.AbstractVitamin B12 and folic acid deficiencies are particularly frequent conditions in older people. Since these metabolic disorders represent relevant dyscognitive factors, the assessment of vitamin B12 and folic acid levels is essential in the diagnostic approach of cognitive disorders, such as mild cognitive impairment and dementia in an outpatient memory clinic. This article summarizes the relevant diagnostic and therapeutic aspects of vitamin B12 and folic acid deficiencies and their effects on cognition. The literature review is supplemented by a data analysis of a naturalistic cohort of 250 patients from this outpatient memory clinic.
In many international studies, rates of completed suicide and suicide attempts have a seasonal pa... more In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the sun striking a surface area on earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
Abstract The neural response to faces of attachment figures compared with unfamiliar faces still ... more Abstract The neural response to faces of attachment figures compared with unfamiliar faces still remains elusive. In particular, the modulation of the neural response by the organized (secure, insecure) compared with disorganized attachment representation of the subject investigated is unknown. For the present study, 38 healthy participants (age range, 21–71 years) were recruited. Three attachment groups (secure, n = 14; insecure, n = 15; disorganized, n = 9) were assessed using the Adult Attachment Projective. The participants were shown pictures of the faces of attachment figures (romantic partner/parents) and unfamiliar faces in a blocked factorial design, using functional magnetic resonance imaging. Showing pictures of attachment figures activated parts of a neural social judgment network, important for inferring others' affective and cognitive mental states (e.g., inferior parietal lobe/superior temporal gyrus) in securely attached healthy individuals. In contrast, disorganized attached individuals with the experience of unresolved attachment trauma in their biography showed deactivations in these areas.
Hippocampal thinning and carrying the ε4 allele of the apolipoprotein E (APOE) are associated wit... more Hippocampal thinning and carrying the ε4 allele of the apolipoprotein E (APOE) are associated with reduced cognitive performance in older people. Although cognitive impairment is also frequent during and after depressive episodes, it may occur irrespective of age, which makes it difficult to determine, whether this symptom indicates a risk for or shared mechanisms with neurodegeneration. We therefore investigated the influence of genetic and brain imaging risk factors for dementia on cognitive impairment in young people with major depressive disorder. We used magnetic resonance imaging, APOE genotyping and neurocognitive assessments to examine young adults (mean age: 29.1 ± 6.3 years) with major depressive disorder and a current depressive episode, presenting with or without cognitive deficits. Neither hippocampal thickness nor APOE genotype predicted cognitive impairment. Patients with objective cognitive deficits reported a greater number of previous depressive episodes. Our results have to be interpreted with caution. The small sample size could have prevented the detection of effects. Complementing research methods and investigations across the life span would be necessary to reveal possible interactions between risk factors for dementia, neurodegeneration, depression, and age. In young adults, recurrent depressive episodes may increase the likelihood for cognitive deficits, while common risk factors for dementia do not.
American journal of Alzheimer's disease and other dementias, 2018
Diagnostic assessments for dementia include the evaluation of subjective memory impairment, demen... more Diagnostic assessments for dementia include the evaluation of subjective memory impairment, dementia worries, or depressive symptoms. Data on the predictive value of these factors remain unclear, and varying help-seeking behavior may contribute to this finding. We investigate whether differentiating help-seeking motivation from other psychological factors associated with cognitive impairment would enhance the prediction of diagnostic outcomes in a memory clinic. We obtained information on help-seeking motivation from 171 patients who underwent routine diagnostic assessments. Utilizing a discriminant correspondence analysis, our results indicate that extrinsic motivation increases the likelihood of receiving a dementia diagnosis, whereas depression or the duration of deficits carries discriminatory information to further guide the differentiation of prodromal dementia. Recognizing motivational aspects of help-seeking behavior can complement the clinical evaluation of cognitive perfor...
Cognitive deficits are common in patients with a depressive episode although the predictors for t... more Cognitive deficits are common in patients with a depressive episode although the predictors for their development and severity remain elusive. We investigated whether subjective and objective cognitive impairment in young depressed adults would be associated with cortical thinning in medial temporal subregions. High-resolution magnetic resonance imaging, cortical unfolding data analysis, and comprehensive assessments of subjective and objective cognitive abilities were performed on 27 young patients with a depressive episode (mean age: 29.0 ± 5.8 years) and 23 older participants without a history of a depressive disorder but amnestic mild cognitive impairment (68.5 ± 6.6 years) or normal cognition (65.2 ± 8.7 years). Thickness reductions in parahippocampal, perirhinal and fusiform cortices were associated with subjective memory deficits only among young patients with a depressive episode and a measurable cognitive impairment. Long-term longitudinal data would be desirable to determi...
We present a 56-year-old patient suffering from frontotemporal dementia with parkinsonism linked ... more We present a 56-year-old patient suffering from frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). The history included a three-generation pedigree and the patient was found to be a mutation carrier. The diagnosis was hindered by late appearance of the hypokinetic movement disorder. For clinicians, it is important to consider rare neurodegenerative disease variants in early-onset familial dementia syndromes with behavioral, cognitive, and motor symptoms.
Driving ability in the elderly and cognitively impaired is of growing demographic relevance. Driv... more Driving ability in the elderly and cognitively impaired is of growing demographic relevance. Driving represents a complex task for which multiple central resources are needed. In mild cognitive impairment and dementia, we need to closely monitor driving ability, as it gets irrecoverably lost in the course of the disease. In normal aging, people are often able to self-regulate driving behavior with respect to their medical conditions. Some studies demonstrated that older drivers perform well compared with younger drivers. Others suggest a decline of driving ability in the process of normal aging and an increasing involvement of older drivers in car crashes. However, these findings have been questioned because of several possible biases. Therefore, unnecessary driving restrictions need to be avoided. The reliable evaluation of driving ability requires a specialist assessment with detailed neurocognitive evaluation, investigation of medical history and medical history by proxy, as well...
American journal of Alzheimer's disease and other dementias, 2017
Patients with amnestic mild cognitive impairment (aMCI) are at risk for developing Alzheimer'... more Patients with amnestic mild cognitive impairment (aMCI) are at risk for developing Alzheimer's disease. Due to their prominent memory impairment, structural magnetic resonance imaging (MRI) often focuses on the hippocampal region. However, recent positron-emission tomography data suggest that within a network of frontal and temporal changes, patients with aMCI show metabolic alterations in the precuneus, a key region for higher cognitive functions. Using high-resolution MRI and whole-brain cortical thickness analyses in 28 patients with aMCI and 25 healthy individuals, we wanted to investigate whether structural changes in the precuneus would be associated with cortical thickness reductions in frontal and temporal brain regions in patients with aMCI. In contrast to healthy people, patients with aMCI showed an association of cortical thinning in the precuneus with predominantly left-hemispheric thickness reductions in medial temporal and frontal cortices. Our data highlight struc...
Alzheimer’s disease (AD) patients show better everyday functioning in a familiar setting, but the... more Alzheimer’s disease (AD) patients show better everyday functioning in a familiar setting, but they have a reduced ability to access con-textual details and episodes associated with a familiar person or environment. This suggests a dysfunction in the neural networks associated with stimulus identification. Using functional magnetic resonance imaging, we investigated the neural activity during the recognition of per-sonally familiar and unfamiliar faces and places among AD patients and elderly controls. We did not find a group difference in the neural activity within brain areas important for perceptual familiarity recognition. Patients showed reduced activation for familiar stimuli in pre-frontal brain areas known to be important for retrieving contextual information for a stimulus when compared with controls. These changes may contribute to how AD patients experience a personally familiar face or place.
Bei der stationären Versorgung betagter Covid-19-Patientinnen und -Patienten muss sich das Klinik... more Bei der stationären Versorgung betagter Covid-19-Patientinnen und -Patienten muss sich das Klinikpersonal des Risikos eines Post-Covid-Delirs bewusst sein. Interdisziplinäre Ansätze sind der Schlüssel zu guten Behandlungsergebnissen, einer Verbesserung der kognitiven Prognose nach Delir sowie einer Begrenzung von Hospitalisierungszeiten. Neben pharmakologischen und nicht-pharmakologischen Therapieaspekten spielen hier strukturelle Rahmenbedingungen und die altersmedizinische Expertise am Standort eine entscheidende Rolle.
Investigating retinal thickness may complement existing biological markers for dementia and other... more Investigating retinal thickness may complement existing biological markers for dementia and other neurodegenerative diseases. Although retinal thinning is predictive for cognitive decline, it remains to be investigated if and how this feature aligns with neurodegeneration elsewhere in the brain, specifically in early disease stages.
Cognitive deficits occur frequently among older people. Because the underlying aetiologies may be... more Cognitive deficits occur frequently among older people. Because the underlying aetiologies may be heterogeneous, diagnostic assessments include clinical and neuropsychological evaluations, as well as the examination of biological markers, such as those derived from brain imaging and cerebrospinal fluid analyses. In many cases, detecting neurodegeneration due to Alzheimer’s disease is a main target, given the disease’s epidemiological importance and the value of early intervention strategies. Familial aggregation of the disease illustrates that even its common sporadic variant is highly heritable. However, important risk polymorphisms, such as the ε4 allele of the apolipoprotein E gene (APOE4), exert their influence on disease development and onset within a complex individual pattern of other genetic risk polimorphisms, but they may not be commercially detectable or even known yet. Therefore, a first-degree family history of Alzheimer’s disease (FH) is a clinically accessible composite characteristic that can be used to approximately account for these risks’ effect on brain structure and metabolism. Relatively little is known about how genetic risks modulate cognitive deterioration and help-seeking behaviour among non-demented people. Understanding the motivational aspects of health-care utilization is important to provide adequate access to all people at risk for cognitive decline and dementia. We therefore investigated whether FH and other mediators predict memory clinic referrals by primary care physicians. We obtained detailed neurocognitive and clinical data from 229 non-demented people (mean age SD: 67.8 10.4 years; range: 44–90 years; 56.3% women; Mini-Mental State Examination: 28.2 1.9) who had been recruited through our university memory clinic. These individuals presented for first-time clinical evaluation after referrals by primary care physicians. Subjects provided written informed consent for inclusion in this study, and the university’s ethics committee approved the study. All subjects underwent routine brain imaging, and 22.7% consented to APOE genotyping (APOE4 allele frequency: 40.4%). Based on the data level, logistic regression, univariate ANCOVA, or multivariate ANCOVA was used to analyze group differences. We modelled FH (positive/negative) and APOE4 allele carrier status (presence/absence of the allele) as between-group factors; age, sex, and educational status were covariates where appropriate. Age was a continuous variable, whereas educational status was operationalized as being a university graduate (39.3%; 16.7 2.3 years of education) or having completed a non-academic apprenticeship (60.7%; 12.5 1.4 years of education). We used SPSS Statistics for Windows version 24.0 (IBM Corp., Armonk, NY, USA) for all analyses. Significance level was set at 0.05. Female sex (B = 0.845; Exp(B) = 2.33; 95% confidence interval (CI): 1.17–4.65; SE = 0.35; P = 0.016), younger age (B = 0.053; Exp(B) = 1.06; 95%CI: 1.02–1.09; SE = 0.02; P = 0.003), and higher educational status (B = 0.930; Exp(B) = 2.54; 95%CI: 1.21–5.32; SE = 0.38; P = 0.014) predicted active referral requests from patients rather than referrals primarily motivated by the primary care physician. APOE4 did not predict a referral request (B = 0.384; Exp(B) = 1.47; 95%CI: 0.29–7.33; SE = 0.82; P = 0.64). There was a notable trend for FH (B = 0.735; Exp(B) = 2.09; 95%CI: 0.96–4.53; SE = 0.40; P = 0.063) predicting an active request, but there was no association between FH and agecorrected memory performance on the Consortium to Establish a Registry of Alzheimer’s Disease assessment battery (F = 0.04; degrees of freedom (d.f.) = 1; P = 0.843) or the Mini-Mental State Examination (F = 2.57, d.f. = 1, P = 0.110). There was also no difference in the Mini-Mental State Examination with regard to age (F = 2.10, d.f. = 1, P = 0.149) or sex (F = 0.05, d.f. = 1, P = 0.821), but people with higher educational status performed better on this screening test (F = 10.05, d.f. = 1, P = 0.002). Educational status was not a significant predictor of reporting fear of becoming demented (F = 0.70;
Objective: Cognitive reserve influences age of onset, speed of progression, and clinical manifest... more Objective: Cognitive reserve influences age of onset, speed of progression, and clinical manifestations of Alzheimer’s disease. We investigated whether cognitive reserve interacts with clinical and neuropsychological parameters in mild cognitive impairment (MCI). Methods: In this cross-sectional study, we recruited 273 people (70.6 ± 10.1 years, 54.6% women) suffering from subjective memory complaints ( n = 65), MCI ( n = 121), or dementia ( n = 87). Patients underwent neuropsychological evaluation, laboratory testing, and brain imaging. Additionally, we obtained information on years of education and help-seeking motivation. Results: MCI patients with a university degree were significantly older than those without (71.6 ± 9.6 vs. 66.9 ± 10.3, p = 0.02). University-educated MCI patients demonstrated superior performance in verbal fluency. Intrinsic help-seeking motivation (self-referral) was associated with higher cognitive reserve. Female MCI patients presented with greater intrinsi...
Differentiating mild cognitive impairment due to a depressive episode from early neurodegeneratio... more Differentiating mild cognitive impairment due to a depressive episode from early neurodegeneration is challenging among older people. Although neuropsychological tests are routine diagnostic assessments in the evaluation of cognitive decline, in contrast to dementia syndromes, they are often perceived as non-specific in the differentiation of affective and neurodegenerative mild cognitive impairment. Furthermore, depression may represent not only a risk factor for developing dementia but also a prodromal symptom of incipient neurodegeneration. In a university memory disorder clinic setting, we investigated 90 middle-aged and older individuals (57.8% women) suffering from mild cognitive impairment, presenting with or without current or previous depressive disorder. Using discriminance analysis and a multivariate analysis of variance, we show that impairments in executive functioning and attention were predictive towards cognitive impairment developed during a depressive episode. Reduced verbal fluency was also predictive towards depression-associated cognitive impairment, whereas memory was relatively preserved in these patients. Our data suggest that in addition to biological markers, specific neuropsychological profiles can be helpful to separate different etiologies of mild cognitive impairment.
There are frequent discussions about the challenges of teaching in medical school, often focusing... more There are frequent discussions about the challenges of teaching in medical school, often focusing on technological aspects or time constraints. The retirement of one of my mentors reminded me that being an inspirational teacher is also important for our students' personal and professional development.
Comprehensive neuropsychological assessments, composed of specific tests targeting different aspe... more Comprehensive neuropsychological assessments, composed of specific tests targeting different aspects of cognition, are standard diagnostic tools to characterise the singleor multidomain impairments due to neurodegeneration, depression, or other brain disorders. Individual test results are frequently corrected for age-related changes in performance, and for the years of formal education, a proxy measure for cognitive reserve, that also comprises occupational attainment and intelligence. Education correction for neurocognitive tests could influence a physician’s decision how to diagnose and treat an individual, and has been used to reclassify demented and nondemented individuals in diagnostic assessments. Others point to education differences in European and American populations to explain heterogeneous performances in a common screening test for cognitive impairment. Both scenarios imply that we expect a well-educated person to perform better, reflected by a correlation between the years of formal education and cognitive abilities. We hypothesised that generational differences in education opportunities would challenge this assumption. In the 20th century, many societies experienced substantial changes in education opportunities, specifically regarding access to university education. This is reflected by an increasing percentage of university students in these populations and a strong shift in the ratio of men and women attending the institutions. In Germany for example, ‘universities of applied sciences’ have complemented the higher education sector since the 1970s, increasing tertiary education possibilities in addition to other quantitative changes in the education system. Furthermore, over the course of the last century, high tertiary education inequality due to social class effects has been substantially declining, specifically for women. We investigated 276 people (age range 44–94 years, median: 73 years, 124 male, 152 female), presenting for the first time to a German university memory clinic with cognitive impairment in the spectrum from subjective complaints to dementia. Written informed consent was obtained in accordance with the university’s ethics committee requirements. In addition to an interview (with caregiver, if available) and examination by an experienced physician, all patients underwent routine laboratory testing, magnetic resonance brain imaging and detailed neuropsychological assessments, in line with standard guidelines for how to evaluate cognitive impairment. We performed the statistical analyses using SPSS 24.0 (IBM, Armonk, NY, USA), with a significance level of P < 0.05, two-sided, for all analyses. Participants reporting university education (n = 101) compared with all other individuals (n = 175) were more likely to be older, male, and intrinsically motivated for diagnostic assessments, possibly reflecting the protective effect of cognitive reserve, gender differences in education opportunities, and greater dementia worries. We also found weak to moderate correlations between the years of formal education and a multiple choice vocabulary test, a common measure of premorbid intelligence. The correlation strength shows a notable trend for linear decline with increasing age (from Pearson’s r = 0.60, P = 0.01 among our youngest subjects to Pearson’s r = 0.30, P = 0.02 in our oldest participants, Fisher’s z-transformation: z = 1.38, P = 0.08). However, this can only be detected among subjects without university education (patients younger than 65 years: Pearson’s r = 0.39, P < 0.01; patients older than 65 years: Pearson’s r = 0.12, P = 0.28, z = 1.50, P = 0.07), but not among those individuals with university education (patients younger than 65 years Pearson’s r = 0.20, P = 0.46; patients older than 65 years: Pearson’s r = 0.30, P = 0.02, z = 0.35, P = 0.37). When investigating patients with dementia only, we did not observe the effect. The multiple choice vocabulary test is a valid measure of global premorbid intelligence, appropriately insensitive for the influence of neuropsychiatric disease. Considering the test’s limitations, our data would be in line with reduced validity in the case of severe brain disease. However, neither aging nor the presence of cognitive impairment per se sufficiently explained the observed results. We may speculate that older
ZusammenfassungVitamin-B12- und Folsäuremangelzustände sind insbesondere im höheren Lebensalter h... more ZusammenfassungVitamin-B12- und Folsäuremangelzustände sind insbesondere im höheren Lebensalter häufig. Da derartige Mangelzustände relevant dyskognitive Faktoren darstellen, ist ihre Bestimmung in der diagnostischen Abklärung kognitiver Störung bedeutsam und unverzichtbarer Bestandteil der Routinediagnostik in einer Gedächtnisambulanz. Wir geben einen Überblick über den klinischen Stellenwert von Vitamin-B12- und Folsäuremangelzuständen im Kontext kognitiver Störungen und über diesbezüglich relevante diagnostische und therapeutische Aspekte. Die Literaturübersicht wird durch eine Datenanalyse einer Kohorte von 250 Patienten aus unserer Gedächtnisambulanz ergänzt.AbstractVitamin B12 and folic acid deficiencies are particularly frequent conditions in older people. Since these metabolic disorders represent relevant dyscognitive factors, the assessment of vitamin B12 and folic acid levels is essential in the diagnostic approach of cognitive disorders, such as mild cognitive impairment and dementia in an outpatient memory clinic. This article summarizes the relevant diagnostic and therapeutic aspects of vitamin B12 and folic acid deficiencies and their effects on cognition. The literature review is supplemented by a data analysis of a naturalistic cohort of 250 patients from this outpatient memory clinic.
In many international studies, rates of completed suicide and suicide attempts have a seasonal pa... more In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the sun striking a surface area on earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
Abstract The neural response to faces of attachment figures compared with unfamiliar faces still ... more Abstract The neural response to faces of attachment figures compared with unfamiliar faces still remains elusive. In particular, the modulation of the neural response by the organized (secure, insecure) compared with disorganized attachment representation of the subject investigated is unknown. For the present study, 38 healthy participants (age range, 21–71 years) were recruited. Three attachment groups (secure, n = 14; insecure, n = 15; disorganized, n = 9) were assessed using the Adult Attachment Projective. The participants were shown pictures of the faces of attachment figures (romantic partner/parents) and unfamiliar faces in a blocked factorial design, using functional magnetic resonance imaging. Showing pictures of attachment figures activated parts of a neural social judgment network, important for inferring others' affective and cognitive mental states (e.g., inferior parietal lobe/superior temporal gyrus) in securely attached healthy individuals. In contrast, disorganized attached individuals with the experience of unresolved attachment trauma in their biography showed deactivations in these areas.
Hippocampal thinning and carrying the ε4 allele of the apolipoprotein E (APOE) are associated wit... more Hippocampal thinning and carrying the ε4 allele of the apolipoprotein E (APOE) are associated with reduced cognitive performance in older people. Although cognitive impairment is also frequent during and after depressive episodes, it may occur irrespective of age, which makes it difficult to determine, whether this symptom indicates a risk for or shared mechanisms with neurodegeneration. We therefore investigated the influence of genetic and brain imaging risk factors for dementia on cognitive impairment in young people with major depressive disorder. We used magnetic resonance imaging, APOE genotyping and neurocognitive assessments to examine young adults (mean age: 29.1 ± 6.3 years) with major depressive disorder and a current depressive episode, presenting with or without cognitive deficits. Neither hippocampal thickness nor APOE genotype predicted cognitive impairment. Patients with objective cognitive deficits reported a greater number of previous depressive episodes. Our results have to be interpreted with caution. The small sample size could have prevented the detection of effects. Complementing research methods and investigations across the life span would be necessary to reveal possible interactions between risk factors for dementia, neurodegeneration, depression, and age. In young adults, recurrent depressive episodes may increase the likelihood for cognitive deficits, while common risk factors for dementia do not.
American journal of Alzheimer's disease and other dementias, 2018
Diagnostic assessments for dementia include the evaluation of subjective memory impairment, demen... more Diagnostic assessments for dementia include the evaluation of subjective memory impairment, dementia worries, or depressive symptoms. Data on the predictive value of these factors remain unclear, and varying help-seeking behavior may contribute to this finding. We investigate whether differentiating help-seeking motivation from other psychological factors associated with cognitive impairment would enhance the prediction of diagnostic outcomes in a memory clinic. We obtained information on help-seeking motivation from 171 patients who underwent routine diagnostic assessments. Utilizing a discriminant correspondence analysis, our results indicate that extrinsic motivation increases the likelihood of receiving a dementia diagnosis, whereas depression or the duration of deficits carries discriminatory information to further guide the differentiation of prodromal dementia. Recognizing motivational aspects of help-seeking behavior can complement the clinical evaluation of cognitive perfor...
Cognitive deficits are common in patients with a depressive episode although the predictors for t... more Cognitive deficits are common in patients with a depressive episode although the predictors for their development and severity remain elusive. We investigated whether subjective and objective cognitive impairment in young depressed adults would be associated with cortical thinning in medial temporal subregions. High-resolution magnetic resonance imaging, cortical unfolding data analysis, and comprehensive assessments of subjective and objective cognitive abilities were performed on 27 young patients with a depressive episode (mean age: 29.0 ± 5.8 years) and 23 older participants without a history of a depressive disorder but amnestic mild cognitive impairment (68.5 ± 6.6 years) or normal cognition (65.2 ± 8.7 years). Thickness reductions in parahippocampal, perirhinal and fusiform cortices were associated with subjective memory deficits only among young patients with a depressive episode and a measurable cognitive impairment. Long-term longitudinal data would be desirable to determi...
We present a 56-year-old patient suffering from frontotemporal dementia with parkinsonism linked ... more We present a 56-year-old patient suffering from frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). The history included a three-generation pedigree and the patient was found to be a mutation carrier. The diagnosis was hindered by late appearance of the hypokinetic movement disorder. For clinicians, it is important to consider rare neurodegenerative disease variants in early-onset familial dementia syndromes with behavioral, cognitive, and motor symptoms.
Driving ability in the elderly and cognitively impaired is of growing demographic relevance. Driv... more Driving ability in the elderly and cognitively impaired is of growing demographic relevance. Driving represents a complex task for which multiple central resources are needed. In mild cognitive impairment and dementia, we need to closely monitor driving ability, as it gets irrecoverably lost in the course of the disease. In normal aging, people are often able to self-regulate driving behavior with respect to their medical conditions. Some studies demonstrated that older drivers perform well compared with younger drivers. Others suggest a decline of driving ability in the process of normal aging and an increasing involvement of older drivers in car crashes. However, these findings have been questioned because of several possible biases. Therefore, unnecessary driving restrictions need to be avoided. The reliable evaluation of driving ability requires a specialist assessment with detailed neurocognitive evaluation, investigation of medical history and medical history by proxy, as well...
American journal of Alzheimer's disease and other dementias, 2017
Patients with amnestic mild cognitive impairment (aMCI) are at risk for developing Alzheimer'... more Patients with amnestic mild cognitive impairment (aMCI) are at risk for developing Alzheimer's disease. Due to their prominent memory impairment, structural magnetic resonance imaging (MRI) often focuses on the hippocampal region. However, recent positron-emission tomography data suggest that within a network of frontal and temporal changes, patients with aMCI show metabolic alterations in the precuneus, a key region for higher cognitive functions. Using high-resolution MRI and whole-brain cortical thickness analyses in 28 patients with aMCI and 25 healthy individuals, we wanted to investigate whether structural changes in the precuneus would be associated with cortical thickness reductions in frontal and temporal brain regions in patients with aMCI. In contrast to healthy people, patients with aMCI showed an association of cortical thinning in the precuneus with predominantly left-hemispheric thickness reductions in medial temporal and frontal cortices. Our data highlight struc...
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Papers by Markus Donix